Lipoproteins human studies

Krauss, R.M., Eckel, R.H., Howard, B., Appel, L.J., Daniels, S.R., Deckelbaum, R.J., Erdman, J.W., Jr., Kris-Etherton, P., Goldberg, I.J., Kotchen, T.A., Lichtenstein, A.H., Mitch, W.E., et al. 2000. AHA dietary guidelines. Revision 2000 A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102, 2296-2311. Kris-Etherton, P.M. and Yu, S. 1997. Individual fatty acid effects on plasma lipids and lipoproteins Human studies. Am. J. Clin. Nutr. 65(Suppl. 5), 1628S-1644S. 

KrlS Etherton, P. M., and Yu, S. (1997). Individual fatty acid effects on plasma lipids and lipoproteins Human studies. Am.. CfiM. Nutr. 65, 1628 -1644S-... 

Kris-Etherton P, Yu S. Individual fatty acids on plasma lipids and lipoproteins human studies. Am J Clin Nutr. 1997 65(suppl) 1628S-1644S. 

Harris, W. 1997. Am. J. Clin. Nutr., 65, 1645S-1654S. n-3 fatty acids and serum lipoproteins human studies. 

The rotational mobility of human low-density (LDL) and very-low-density (VLDL) lipoproteins was studied as a function of viscosity and temperature in the range of —90 to — 50°C.(86)The rotational behavior for LDL is represented by a single correlation time, consistent with the overall rotation of a spherical rigid particle as the source of the phosphorescence depolarization. For VLDL, internal peptide motions dominate the depolarization profile. 

Cl. Camejo, G., Suarez, Z. M., and Munoz, V., The apolipoproteins of human plasma high density lipoprotein a study of their lipid-binding capacity and interaction with lipid monolayers. Biochim. Biophys. Acta 218, 155-166 (1970). 

B16. Barter, P. J., and Lally, J. I., In vitro exchanges of esterified cholesterol between serum lipoprotein fractions Studies of humans and rabbits. Metabolism 28, 230-236 (1979). 

Since the beneficial effects of lipoprotein were thought to be related to phospholipid content, a lipid emulsion with 10% phospholipids was developed and tested in animal as well as human studies (Gordon et al., 2003). 

The quantitative relationship between cholesterol intake and cholesterol levels is still controversial, especially because in humans, there appears to be a high individual variability in processing of dietary cholesterol. However, numerous animal and human studies support the concept that dietary cholesterol can raise LDL-cholesterol levels and change the size and composition of these particles as well. LDL particles become larger in size and enriched in cholesterol esters. Mechanisms contributing to these events include an increase in hepatic synthesis of apoB-containing lipoproteins, increased conversion of VLDL remnants to LDL, or a decrease in the fractional catabolic rate for LDL. Reduced LDL receptor activity due to an increase in hepatic cholesterol content, secondary to excess dietary cholesterol, may lead to a decreased uptake of both LDL and VLDL remnants. 

Numerous animal and human studies suggest that dietary cholesterol and certain saturated fatty acids increase serum as well as LDL-cholesterol concentrations. Even though humans with elevated serum cholesterol levels may be at risk, evidence also is mounting to suggest that the complicated processes that occur during atherosclerosis involve not only the participation of modified lipoproteins, but also low level and chronic inflammation and related disorders of the immune... 

The effects of palm oil on serum lipids and lipoproteins recorded in animal studies have similarly been observed in several human studies. In some early human studies (152, 153), it was reported that subjects on a palm oil diet had elevated plasma and low-density lipoprotein cholesterol LDL-C levels compared to a diet containing a polyusaturated fat. However, on a critical reassessment of these and other relevant studies (154), it was found that plasma cholesterol levels after the palm oil period were actually lower than at the point of entry of the experiments when the subjects were on their habitual diets. 

During the early 1950s, it was reported that phytosterols lower serum cholesterol (173-175). This effect was appreciated as a possible protection strategy against car-divascular disease risk after the results of several convincing animal and human studies (176-184). Studies have shown that a daily intake of 2-g phytosterol or phytostanol causes 40-50% reduction in the dietary cholesterol absorption, 6-10% reduction in total serum cholesterol, and 8-14% reduction in the semm low-density lipoprotein cholesterol (37, 185-187). 

Phospholipid transfer protein (PLTP) (carrier protein that shuttles between lipoproteins to redistribute lipids) deficiency in mice is associated with decreased atherosclerosis despite decreased HDL levels. Two mechanisms are involved decreased Apo B-containing lipoprotein production and levels, and increased antioxidation potential. Human studies indicated that PLTP activity positively correlated with aging, obesity, DM, and CAD (reviewed in ref. 429). PLTP mRNA protein expression and activity was increased by cholesterol loading of macrophages. PLTP increased HDL binding to biglycan, suggesting a role in lipoprotein retention on ECM (430). 

Patterns of cholesterol biosynthesis and transport in the baboon parallel those observed in man (Kritchevsky et al., 1965). Peak specific activity of serum-free cholesterol synthesized from mevalonic acid-2-is reached within 4—10 hours and the free and esterified forms equilibrate by 72 hours. Peak specific activities of exogenously labeled serum-free and ester cholesterol are observed at three days. The specific activity of the total cholesterol of the serum a and lipoproteins is equal over a 10-day period, but there is the possibility that the specific activities of the free and ester cholesterol moieties of the serum oc and jS lipoproteins differ. The lipoprotein cholesterol findings are similar to results reported from similar human studies (Gidez and Eder, 1963). The equilibration of serum and tissue cholesterol is reached at about two weeks in the dog (Gould, 1952) and rat (Chevallier, 1953) and one month in man (Chobanian and Hollander, 1962). 

Mechanism of the hypocholesteremic effect remains in doubt, but may involve inhibition of release of lipoprotein cholesterol from the liver Kritchevsky et al ° found probucol to reduce plasma cholesterol and atheroma fformation in cholesterol-fed rabbits. Probucol apparently was well tolerated in the human studies. 

As yet, no human diseases have been identified as a result of FATPl mutations. However, genetic polymorphisms in the human FATPl gene have been linked to dyslipidemia. An A/G exchange at position +48 in intron 8 of the FATPl gene has been shown to result in increased TG concentrations in female but not in male subjects. In a second study, the same polymorphism was linked to increased postprandial TG concentrations and smaller low density lipoprotein (LDL) particles. To date, it is still unknown if this polymorphism is associated with altered levels of FATPl expression and/or function. 

The antioxidant activities of carotenoids and other phytochemicals in the human body can be measured, or at least estimated, by a variety of techniques, in vitro, in vivo or ex vivo (Krinsky, 2001). Many studies describe the use of ex vivo methods to measure the oxidisability of low-density lipoprotein (LDL) particles after dietary intervention with carotene-rich foods. However, the difficulty with this approach is that complex plant foods usually also contain other carotenoids, ascorbate, flavonoids, and other compounds that have antioxidant activity, and it is difficult to attribute the results to any particular class of compounds. One study, in which subjects were given additional fruits and vegetables, demonstrated an increase in the resistance of LDL to oxidation (Hininger et al., 1997), but two other showed no effect (Chopra et al, 1996 van het Hof et al., 1999). These differing outcomes may have been due to systematic differences in the experimental protocols or in the populations studied (Krinsky, 2001), but the results do indicate the complexity of the problem, and the hazards of generalising too readily about the putative benefits of dietary antioxidants. 

As has already been stated, the carotenoids are lipophilic and are therefore absorbed and transported in association with the lipoprotein particles. In theory, this fortuitous juxtaposition of lipid and carotenoid should confer protection on the lipid through the antioxidant properties of the carotenoid. No doubt some antioxidant protection is afforded by the presence of the carotenoids derived from the diet. However, with one or two exceptions, human supplementation studies have not supported a role for higher dose carotenoid supplements in reducing the susceptibility of the low-density lipoproteins to oxidation, either ex vivo or in vivo (Wright et al, 2002 Hininger et al, 2001 Iwamoto et al, 2000). 

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